RESUMEN
BACKGROUND: Atypical haemolytic uremic syndrome (aHUS) is an uncommon form of thrombotic microangiopathy (TMA). However, it remains difficult to diagnose the disease early, given its non-specific and overlapping presentation to other conditions such as thrombotic thrombocytopenic purpura and typical HUS. It is also important to identify the underlying causes and to distinguish between primary (due to a genetic abnormality leading to a dysregulated alternative complement pathway) and secondary (often attributed by severe infection or inflammation) forms of the disease, as there is now effective treatment such as monoclonal antibodies against C5 for primary aHUS. However, primary aHUS with severe inflammation are often mistaken as a secondary HUS. We presented an unusual case of adult-onset Still's disease (AOSD) with macrophage activation syndrome (MAS), which is in fact associated with anti-complement factor H (anti-CFH) antibodies related aHUS. Although the aHUS may be triggered by the severe inflammation from the AOSD, the presence of anti-CFH antibodies suggests an underlying genetic defect in the alternative complement pathway, predisposing to primary aHUS. One should note that anti-CFH antibodies associated aHUS may not always associate with genetic predisposition to complement dysregulation and can be an autoimmune form of aHUS, highlighting the importance of genetic testing. CASE PRESENTATION: A 42 years old man was admitted with suspected adult-onset Still's disease. Intravenous methylprednisolone was started but patient was complicated with acute encephalopathy and low platelet. ADAMTS13 test returned to be normal and concurrent aHUS was eventually suspected, 26 days after the initial thrombocytopenia was presented. Plasma exchange was started and patient eventually had 2 doses of eculizumab after funding was approved. Concurrent tocilizumab was also used to treat the adult-onset Still's disease with MAS. The patient was eventually stabilised and long-term tocilizumab maintenance treatment was planned instead of eculizumab following haematology review. Although the aHUS may be a secondary event to MAS according to haematology opinion and the genetic test came back negative for the five major aHUS gene, high titre of anti-CFH antibodies was detected (1242 AU/ml). CONCLUSION: Our case highlighted the importance of prompt anti-CFH antibodies test and genetic testing for aHUS in patients with severe AOSD and features of TMA. Our case also emphasized testing for structural variants within the CFH and CFH-related proteins gene region, as part of the routine genetic analysis in patients with anti-CFH antibodies associated aHUS to improve diagnostic approaches.
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Síndrome Hemolítico Urémico Atípico , Factor H de Complemento , Enfermedad de Still del Adulto , Humanos , Enfermedad de Still del Adulto/complicaciones , Enfermedad de Still del Adulto/diagnóstico , Enfermedad de Still del Adulto/tratamiento farmacológico , Síndrome Hemolítico Urémico Atípico/complicaciones , Síndrome Hemolítico Urémico Atípico/inmunología , Factor H de Complemento/inmunología , Adulto , Masculino , Autoanticuerpos/sangre , Síndrome de Activación Macrofágica/diagnóstico , Síndrome de Activación Macrofágica/complicaciones , Síndrome de Activación Macrofágica/inmunologíaRESUMEN
BACKGROUND: Few studies have evaluated the impact of subclinical microstructural changes and psychosocial factors on cognitive function in patients with haemophilia. OBJECTIVES: To determine the prevalence and characteristics of cognitive impairment in patients with haemophilia, and identify associated risk factors. METHODS: We recruited haemophilia A or B patients who were aged ≥10 years old from three public hospitals in Hong Kong. A neurocognitive battery was administered to evaluate their attention, memory, processing speed and cognitive flexibility performances. They also underwent magnetic resonance imaging to identify cerebral microbleeds. Validated self-reported questionnaires were administered to assess their mental health status and adherence to prophylactic treatment. General linear modelling was used to investigate the association of neurocognitive outcomes with risks factors, adjusting for age and education attainment. RESULTS: Forty-two patients were recruited (median age 32.0 years; 78.6% haemophilia A; 80.9% moderate-to-severe disease). Six patients (14.3%) had developed cerebral microbleeds. A subgroup of patients demonstrated impairments in cognitive flexibility (30.9%) and motor processing speed (26.2%). Hemarthrosis in the previous year was associated with worse attention (Estimate = 7.62, 95% CI: 1.92-15.33; p = .049) and cognitive flexibility (Estimate = 8.64, 95% CI: 2.52-13.29; p = .043). Depressive (Estimate = 0.22, 95% CI: 0.10-0.55; p = .023) and anxiety (Estimate = 0.26, 95% CI: 0.19-0.41; p = .0069) symptoms were associated with inattentiveness. Among patients receiving prophylactic treatment (71.4%), medication adherence was positively correlated with cognitive flexibility (p = .037). CONCLUSION: A substantial proportion of patients with haemophilia demonstrated cognitive impairment, particularly higher-order thinking skills. Screening for cognitive deficits should be incorporated into routine care. Future studies should evaluate the association of neurocognitive outcomes with occupational/vocational outcomes.
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Disfunción Cognitiva , Hemofilia A , Adulto , Humanos , Hemorragia Cerebral/etiología , Hemorragia Cerebral/patología , Pueblos del Este de Asia , Hemofilia A/complicaciones , Neuroimagen , Factores de Riesgo , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/etiología , Hemofilia B/complicacionesRESUMEN
Coronavirus disease 2019 (COVID-19) is affecting millions of patients worldwide. It is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which belongs to the family Coronaviridae, with 80% genomic similarities to SARS-CoV. Lymphopenia was commonly seen in infected patients and has a correlation to disease severity. Thrombocytopenia, coagulation abnormalities, and disseminated intravascular coagulation were observed in COVID-19 patients, especially those with critical illness and non-survivors. This pandemic has caused disruption in communities and hospital services, as well as straining blood product supply, affecting chemotherapy treatment and haematopoietic stem cell transplantation schedule. In this article, we review the haematological manifestations of the disease and its implication on the management of patients with haematological disorders.
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Coagulación Intravascular Diseminada , Trasplante de Células Madre Hematopoyéticas , Linfopenia , Pandemias , SARS-CoV-2/metabolismo , Trombocitopenia , COVID-19/sangre , COVID-19/mortalidad , COVID-19/terapia , Coagulación Intravascular Diseminada/sangre , Coagulación Intravascular Diseminada/mortalidad , Coagulación Intravascular Diseminada/terapia , Coagulación Intravascular Diseminada/virología , Humanos , Linfopenia/sangre , Linfopenia/mortalidad , Linfopenia/terapia , Linfopenia/virología , Trombocitopenia/sangre , Trombocitopenia/mortalidad , Trombocitopenia/terapia , Trombocitopenia/virologíaRESUMEN
WHAT IS KNOWN AND OBJECTIVE: SLCO1B1 T521>C variant carriers are susceptible to simvastatin-induced myopathy. We report a patient who developed rhabdomyolysis possibly triggered by a drug-drug and/or herb-drug interaction. CASE DESCRIPTION: A 69-year-old man presented with myalgia and weakness progressing to severe rhabdomyolysis. He had been taking 40 mg simvastatin daily for 10 years and recently consumed supplements, including Stevia rebaudiana and linagliptin. Genotyping revealed he carried one copy of SLCO1B1 T521>C and two copies of ABCG2 C421>A. WHAT IS NEW AND CONCLUSION: Despite apparent long-term safe administration, co-ingestion of simvastatin and other CYP3A4 inhibitors may result in severe myopathy in those at increased genetic risk.
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Predisposición Genética a la Enfermedad/genética , Linagliptina/administración & dosificación , Transportador 1 de Anión Orgánico Específico del Hígado/genética , Enfermedades Musculares/inducido químicamente , Enfermedades Musculares/genética , Polimorfismo de Nucleótido Simple/genética , Simvastatina/efectos adversos , Anciano , Inhibidores del Citocromo P-450 CYP3A/administración & dosificación , Interacciones Farmacológicas/genética , Interacciones de Hierba-Droga/genética , Humanos , Masculino , SteviaRESUMEN
This work describes the preparation of quinoline compounds as possible anti-bacterial agents. The synthesized quinoline derivatives show anti-bacterial activity towards Staphylococcus aureus. It is interesting to observe that the synthetic 5,7-dibromo-2-methylquinolin-8-ol (4) shows a similar minimum inhibitory concentration of 6.25µg/mL as compared to that of methicillin (3.125µg/mL) against Staphylococcus aureus.
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Antibacterianos/farmacología , Oxiquinolina/farmacología , Staphylococcus aureus/efectos de los fármacos , Antibacterianos/síntesis química , Antibacterianos/química , Muerte Celular/efectos de los fármacos , Línea Celular , Relación Dosis-Respuesta a Droga , Humanos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Oxiquinolina/síntesis química , Oxiquinolina/química , Relación Estructura-ActividadRESUMEN
BACKGROUND: Although complement component 5 inhibitors (C5is) eculizumab and ravulizumab improve paroxysmal nocturnal hemoglobinuria (PNH) outcomes, patients may experience persistent anemia. This post hoc analysis investigated whether the complement component 3-targeted therapy pegcetacoplan also improved hematologic outcomes and reduced fatigue in patients with PNH and mild/moderate anemia. METHODS: Patients with PNH and hemoglobin ≥10.0 g/dL at baseline of PADDOCK (N = 6), PRINCE (N = 8), and PEGASUS (N = 11) were included. Before receiving pegcetacoplan, PADDOCK and PRINCE patients were C5i-naive; PEGASUS patients had hemoglobin <10.5 g/dL despite stably dosed eculizumab. Hemoglobin concentrations, percentages of patients with concentrations ≥12 g/dL, and sex-specific normalization were assessed at baseline and after 16 weeks of pegcetacoplan, as were absolute reticulocyte counts (ARCs) and normalization and fatigue scores and normalization. RESULTS: From baseline to week 16, mean (SD) hemoglobin concentrations increased in C5i-naive patients (PADDOCK: 10.5 [0.4] to 12.7 [1.1] g/dL; PRINCE: 11.3 [1.0] to 14.0 [1.3] g/dL) and those with suboptimal eculizumab responses (PEGASUS: 10.2 [0.2] to 12.8 [2.6] g/dL). Percentage of patients with hemoglobin ≥12 g/dL increased (PADDOCK: 0 to 60.0% [3 of 5 patients]; PRINCE: 25.0% [2 of 8] to 87.5% [7 of 8]; PEGASUS: 0 to 72.7% [8 of 11]). Sex-specific hemoglobin normalization at week 16 occurred in 40.0% (2 of 5) (PADDOCK), 62.5% (5 of 8) (PRINCE), and 63.6% (7 of 11) (PEGASUS). In all studies, mean ARCs decreased from above normal to normal and ARC normalization increased. Mean Functional Assessment of Chronic Illness Therapy-Fatigue scores improved from below to above or near normal. Two patients had serious adverse events (PEGASUS: post-surgery sepsis, breakthrough hemolysis); breakthrough hemolysis resolved without study discontinuation. CONCLUSION: Patients with PNH and mild/moderate anemia who were C5i-naive or who had suboptimal hemoglobin concentrations despite eculizumab treatment had improved hematologic outcomes and reduced fatigue after initiating or switching to pegcetacoplan. TRIAL REGISTRATION: Trial registration numbers: PADDOCK (NCT02588833), PRINCE (NCT04085601; EudraCT, 2018-004220-11), PEGASUS (NCT03500549).
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Anemia , Anticuerpos Monoclonales Humanizados , Fatiga , Hemoglobinas , Hemoglobinuria Paroxística , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Anemia/tratamiento farmacológico , Anemia/sangre , Anemia/etiología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Biomarcadores/sangre , Complemento C3/metabolismo , Inactivadores del Complemento/uso terapéutico , Fatiga/tratamiento farmacológico , Fatiga/sangre , Fatiga/etiología , Hemoglobinas/análisis , Hemoglobinas/metabolismo , Hemoglobinuria Paroxística/tratamiento farmacológico , Hemoglobinuria Paroxística/sangre , Resultado del TratamientoRESUMEN
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, accounting for around 30-60% of all cases. The management of DLBCL in Asia has several unmet needs due to the diversity of the population, the heterogeneity of local clinical guidelines for DLBCL and the wide disparity in resources and healthcare systems across different regions. Rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP) is widely recognized as the standard first-line treatment for DLBCL; however, alternative regimens are required to improve patient outcomes in challenging subtypes, such as patients with high International Prognostic Index scores, old/frail patients, and patients with double-hit and double-expressor DLBCL or concurrent central nervous system disease. This review article draws from the expertise of practicing hematologists/oncologists in the region, with the aim of integrating data from current scientific evidence to address the unmet needs and unique socioeconomic challenges faced by challenging high risk patient groups in the Asia-Pacific region.
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Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma de Células B Grandes Difuso , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Asia/epidemiología , Ciclofosfamida/uso terapéutico , Vincristina/uso terapéuticoRESUMEN
ABSTRACT: Multiple myeloma (MM) cells are addicted to MYC and its direct transactivation targets IRF4 for proliferation and survival. MYC and IRF4 are still considered "undruggable," as most small-molecule inhibitors suffer from low potency, suboptimal pharmacokinetic properties, and undesirable off-target effects. Indirect inhibition of MYC/IRF4 emerges as a therapeutic vulnerability in MM. Here, we uncovered an unappreciated tumor-suppressive role of C-terminal binding protein 2 (CTBP2) in MM via strong inhibition of the MYC-IRF4 axis. In contrast to epithelial cancers, CTBP2 is frequently downregulated in MM, in association with shortened survival, hyperproliferative features, and adverse clinical outcomes. Restoration of CTBP2 exhibited potent antitumor effects against MM in vitro and in vivo, with marked repression of the MYC-IRF4 network genes. Mechanistically, CTBP2 impeded the transcription of MYC and IRF4 by histone H3 lysine 27 deacetylation (H3K27ac) and indirectly via activation of the MYC repressor IFIT3. In addition, activation of the interferon gene signature by CTBP2 suggested its concomitant immunomodulatory role in MM. Epigenetic studies have revealed the contribution of polycomb-mediated silencing and DNA methylation to CTBP2 inactivation in MM. Notably, inhibitors of Enhance of zeste homolog 2, histone deacetylase, and DNA methyltransferase, currently under evaluation in clinical trials, were effective in restoring CTBP2 expression in MM. Our findings indicated that the loss of CTBP2 plays an essential role in myelomagenesis and deciphers an additional mechanistic link to MYC-IRF4 dysregulation in MM. We envision that the identification of novel critical regulators will facilitate the development of selective and effective approaches for treating this MYC/IRF4-addicted malignancy.
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Oxidorreductasas de Alcohol , Proteínas Co-Represoras , Factores Reguladores del Interferón , Mieloma Múltiple , Proteínas Proto-Oncogénicas c-myc , Animales , Humanos , Ratones , Oxidorreductasas de Alcohol/metabolismo , Oxidorreductasas de Alcohol/antagonistas & inhibidores , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Factores Reguladores del Interferón/metabolismo , Factores Reguladores del Interferón/genética , Mieloma Múltiple/metabolismo , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/patología , Proteínas Proto-Oncogénicas c-myc/metabolismo , Transducción de Señal/efectos de los fármacos , Proteínas Supresoras de Tumor/metabolismo , Proteínas Co-Represoras/antagonistas & inhibidores , Proteínas Co-Represoras/metabolismoRESUMEN
We explore the possible cellular cytotoxic activity of an amphiphilic silicon(IV) phthalocyanine with axially ligated rhodamine B under ambient light experimental environment as well as its in vivo antitumour potential using Hep3B hepatoma cell model. After loading into the Hep3B hepatoma cells, induction of cellular cytotoxicity and cell cycle arrest were detected. Strong growth inhibition of tumour xenograft together with significant tumour necrosis and limited toxicological effects exerted on the nude mice could be identified.
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Antineoplásicos/farmacología , Indoles/química , Indoles/farmacología , Rodaminas/química , Rodaminas/farmacología , Silicio/farmacología , Animales , Antineoplásicos/química , Línea Celular Tumoral , Humanos , Isoindoles , Neoplasias Hepáticas/tratamiento farmacológico , Ratones , Ratones Desnudos , Distribución Aleatoria , Silicio/química , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
CITE was a prospective, noninterventional study in adult patients with chronic immune thrombocytopenia treated with eltrombopag under routine clinical care in Asia-Pacific, the Middle East, and Turkey. Data to assess eltrombopag usage, compliance, and outcomes were collected from May 2017 to December 2020. Platelet response was defined as platelet count ≥50 × 103/µL in the absence of rescue medications and splenectomy. Quality of life was evaluated using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire. Noncompliance was defined as the number of missed doses and number of days where the patient did not follow food instructions. A total of 231 patients were enrolled; the median (range) duration of eltrombopag treatment was 484.5 (1-642) days. Compliance to prescribed eltrombopag dose since the previous routine visit was high at ≥96.0%. Baseline median platelet count was 19.0 × 103/µL, which increased to ≥50 × 103/µL at month 2 and mostly fluctuated between 70 × 103/µL and 100 × 103/µL thereafter. The median time to first platelet response was 1.05 (95% confidence interval: 0.92-1.28) months, and the median (interquartile range) maximum duration of platelet response was 193 (57-456) days. FACIT-F scores improved from a mean (standard deviation) 34.4 (12.1) at baseline to 38.5 (9.1) at month 18. Adverse events occurred in 50.9% of patients (n = 116), the most common being upper respiratory tract infection (8.3%) and headache (6.6%). These findings confirmed the effectiveness of eltrombopag treatment in routine practice and reassured that real-world compliance to eltrombopag-prescribed doses and dietary instructions in Asia-Pacific, the Middle East, and Turkey were in line with current recommendations.
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Púrpura Trombocitopénica Idiopática , Adulto , Humanos , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Púrpura Trombocitopénica Idiopática/inducido químicamente , Turquía , Calidad de Vida , Estudios Prospectivos , Enfermedad Crónica , Hidrazinas/efectos adversos , AsiaRESUMEN
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease characterized by complement-mediated hemolysis. Pegcetacoplan is the first C3-targeted therapy approved for adults with PNH (United States), adults with PNH with inadequate response or intolerance to a C5 inhibitor (Australia), and adults with anemia despite C5-targeted therapy for ≥3 months (European Union). PRINCE was a phase 3, randomized, multicenter, open-label, controlled study to evaluate the efficacy and safety of pegcetacoplan vs control (supportive care only; eg, blood transfusions, corticosteroids, and supplements) in complement inhibitor-naive patients with PNH. Eligible adults receiving supportive care only for PNH were randomly assigned and stratified based on their number of transfusions (<4 or ≥4) 12 months before screening. Patients received pegcetacoplan 1080 mg subcutaneously twice weekly or continued supportive care (control) for 26 weeks. Coprimary end points were hemoglobin stabilization (avoidance of >1-g/dL decrease in hemoglobin levels without transfusions) from baseline through week 26 and lactate dehydrogenase (LDH) change at week 26. Overall, 53 patients received pegcetacoplan (n = 35) or control (n = 18). Pegcetacoplan was superior to control for hemoglobin stabilization (pegcetacoplan, 85.7%; control, 0; difference, 73.1%; 95% confidence interval [CI], 57.2-89.0; P < .0001) and change from baseline in LDH (least square mean change: pegcetacoplan, -1870.5 U/L; control, -400.1 U/L; difference, -1470.4 U/L; 95% CI, -2113.4 to -827.3; P < .0001). Pegcetacoplan was well tolerated. No pegcetacoplan-related adverse events were serious, and no new safety signals were observed. Pegcetacoplan rapidly and significantly stabilized hemoglobin and reduced LDH in complement inhibitor-naive patients and had a favorable safety profile. This trial was registered at www.clinicaltrials.gov as NCT04085601.
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Hemoglobinuria Paroxística , Adulto , Humanos , Hemoglobinuria Paroxística/tratamiento farmacológico , Inactivadores del Complemento/efectos adversos , Hemólisis , Anticuerpos Monoclonales Humanizados/efectos adversos , Hemoglobinas , L-Lactato DeshidrogenasaRESUMEN
Background: The PLASMIC score is a convenient tool for predicting ADAMTS13 activity of <10%. Lactate dehydrogenase (LDH) is widely used as a marker of haemolysis in thrombotic thrombocytopenic purpura (TTP) monitoring, and could be used as a replacement marker for lysis. We aimed to validate the PLASMIC score in a multi-centre Asia Pacific region, and to explore whether LDH could be used as a replacement marker for lysis. Methods: Records of patients with thrombotic microangiopathy (TMA) were reviewed. Patients' ADAMTS13 activity levels were obtained, along with clinical/laboratory findings relevant to the PLASMIC score. Both PLASMIC scores and PLASMIC-LDH scores, in which LDH replaced traditional lysis markers, were calculated. We generated a receiver operator characteristics (ROC) curve and compared the area under the curve values (AUC) to determine the predictive ability of each score. Results: 46 patients fulfilled the inclusion criteria, of which 34 had ADAMTS13 activity levels of <10%. When the patients were divided into intermediate-to-high risk (scores 5â7) and low risk (scores 0â4), the PLASMIC score showed a sensitivity of 97.1% and specificity of 58.3%, with a positive predictive value (PPV) of 86.8% and negative predictive value (NPV) of 87.5%. The PLASMIC-LDH score had a sensitivity of 97.1% and specificity of 33.3%, with a PPV of 80.5% and NPV of 80.0%. Conclusion: Our study validated the utility of the PLASMIC score, and demonstrated PLASMIC-LDH as a reasonable alternative in the absence of traditional lysis markers, to help identify high-risk patients for treatment via plasma exchange.
RESUMEN
Chitosan based microcapsule which encapsulated with phyllanthin was developed by simple coacervation. The composition and surface morphology of phyllanthin containing microcapsules were analyzed by Fourier Transform Infrared spectroscopy and Scanning Electron Microscopy, respectively. The release of phyllanthin from the microcapsules was found to be more than 60% after 120 h. In vitro biological assays demonstrated that these phyllanthin containing microcapsules showed a stronger anti-oxidation potential on both human fibroblasts and keratinocytes as well as a better growth inhibitory activity towards Staphylococcus aureus.
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Cápsulas/química , Fibroblastos/metabolismo , Queratinocitos/metabolismo , Lignanos/química , Microscopía Electrónica de Rastreo/métodos , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus/metabolismo , Antibacterianos/farmacología , Antioxidantes/química , Química Farmacéutica/métodos , Quitosano/química , Diseño de Fármacos , Humanos , Modelos Químicos , Especies Reactivas de Oxígeno , Propiedades de Superficie , Factores de TiempoRESUMEN
Recently, we demonstrated the safety use of calendula oil/chitosan microcapsules as a carrier for both oral and topical deliveries. We also reported the improved biological activity towards skin cells and Staphylococcus aureus of phyllanthin containing chitosan microcapsules. However, the possibility of both oral and topical applications was still necessary to be further studied. Here we investigated that both oral and topical applications of chitosan-based microcapsules were tested using hydrocortisone succinic acid (HSA) and 5-fluorouracil (5-FU), respectively. The drug loading efficiency, particle size, surface morphology and chemical compositions of both drug loaded microcapsules were confirmed by UV-vis spectrophotometer, particle size analyzer, scanning electron microscope and Fourier transform infrared spectroscopy. The in vitro release studies revealed that both HSA and 5-FU could be released form chitosan microcapsules. The mean adrenocorticotropic hormone concentration in HSA loaded microcapsule mice plasma was detected to be lower than that of water control. One hundred micrograms per milliliter of 5-FU containing microcapsules exhibited a stronger growth inhibition towards skin keratinocytes than that of free 5-FU. In vitro drug delivery model demonstrated the delivery of 5-FU from microcapsule treated textiles into nude mice skin. Further uses of the drug loaded microcapsules may provide an efficiency deliverable tool for both oral and topical applications.
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Cápsulas/química , Sistemas de Liberación de Medicamentos/métodos , Administración Oral , Administración Tópica , Animales , Quitosano , Fluorouracilo , Hidrocortisona , Queratinocitos/citología , Ratones , Piel/citología , Piel/efectos de los fármacos , Staphylococcus aureus , Ácido SuccínicoRESUMEN
OBJECTIVE: To delineate the prevalence and associated risk factors of low BMD, osteoporosis/bone fragility and fracture in transfusion-dependent thalassemia (TDT) in the Chinese population in Hong Kong. DESIGN, PATIENTS AND MEASUREMENTS: A retrospective cohort study design was employed. Patients of TDT who had serial Hologic dual-energy X-ray absorptiometry (DXA) from 2010 to 2016 and received regular transfusion for at least 5 years were recruited. Clinical and biochemical data, from 5 years before the first DXA scan, were retrieved from the electronic record system of the Hospital Authority, till 30 June 2020. Low bone mineral density and osteoporosis/bone fragility are defined by the ISCD 2019 position guidelines. RESULTS: Seventy-seven patients were included in the analysis. The fracture prevalence of TDT among the Chinese population in Hong Kong was 15.58%. Up to 55.84% of patients had low bone mineral density, and 5.19% patients had osteoporosis/bone fragility state. The median age at first fracture was 31.73 years (range 24.06-44.18 years). In the regression analysis, a higher log(10) transformation of average ferritin levels over 5 years before the first DXA scan was significantly associated with fracture occurrence regardless of bisphosphonate treatment (OR 310.73, 95% CI 3.99-24183.89, p = .010). Mean average ferritin level over 5 years was 6695.5 ± 2365.7 pmol/L (fracture group) versus 4350.7 ± 3103.2 pmol/L (non-fracture group), p = .016. Hip and spine BMD Z-score did not have statistically significant association with fracture occurrence. CONCLUSION: Iron overloading plays an important role in adverse bone health in TDT. Dual X-ray densitometry is insufficient in predicting fracture risk.
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Fracturas Óseas , Osteoporosis , Talasemia , Adulto , Densidad Ósea , Estudios de Cohortes , Ferritinas , Fracturas Óseas/epidemiología , Fracturas Óseas/etiología , Hong Kong/epidemiología , Humanos , Osteoporosis/epidemiología , Osteoporosis/etiología , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Talasemia/complicaciones , Talasemia/epidemiología , Talasemia/terapia , Adulto JovenRESUMEN
Background: This study aims to identify factors affecting health-related quality of life (HRQoL) in Chinese patients with hemophilia in Hong Kong, and to examine the association between treatment adherence and HRQoL outcomes. Methods: Patients with hemophilia A or B from a non-governmental organization reported their HRQoL and treatment adherence to prophylactic therapy using validated tools. Univariate tests and multivariable regression analysis were used to compare differences in outcomes across clinically relevant subgroups. Results: Fifty-six patients were recruited (mean age 30.4 [17.4] years; majority hemophilia A: 75%; moderate-to-severe severity: 88%). Patients who received prophylactic treatment reported fewer work/school problems (25.8 [18.9] versus 51.5 [26.3]; p = 0.001) than those who received on-demand therapy. The multivariable model showed that older age (B = 0.42, 95% CI = 0.093−0.75) and living in public housing (B = 10.24, 95% CI = 0.70−19.77) were associated with worse HRQoL. Older age was associated with treatment non-adherence (r = 0.66, p < 0.0001). Patients with poor adherence tended to report worse functioning in sports/leisure (r = 0.31, p = 0.033). Conclusions: Our results suggest that patients who were older, had lower education attainment and received on-demand treatment had poorer perception of their health. Improving adherence may lead to better HRQoL. Future work includes evaluating the occupational needs prospectively in this population.
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Hemofilia A , Calidad de Vida , Adulto , Pueblo Asiatico , Hemofilia A/tratamiento farmacológico , Hong Kong/epidemiología , Humanos , Cumplimiento y Adherencia al TratamientoRESUMEN
The use of chitosan as the wall of microcapsule designed for delivery of encapsulated celecoxib is reported. Microcapsules were characterised with respect to size and encapsulation efficiency of celecoxib. In vivo animals demonstrated that both free celecoxib administration and chitosan/celecoxib microcapsules administration lead to a significant inhibition of cyclooxygenase-2 protein expression in the hepatocytes when compared with vehicle control mice. Interestingly, microcapsule containing celecoxib showed a better inhibition of cyclooxygenase-2 protein expression when compared with a simple oral administration of free celecoxib. Gas-chromatography-mass-spectrometry analysis showed that in mice treated with free celecoxib or chitosan/celecoxib microcapsules, their plasma concentration of celecoxib was similar. Microcapsules-based biomaterials as oral drug delivery vehicles may help to improve the absorption efficiency of therapeutic drugs.
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Quitosano/síntesis química , Quitosano/farmacología , Inhibidores de la Ciclooxigenasa 2/síntesis química , Inhibidores de la Ciclooxigenasa 2/farmacología , Pirazoles/síntesis química , Pirazoles/farmacología , Sulfonamidas/síntesis química , Sulfonamidas/farmacología , Celecoxib , Cromatografía de Gases y Espectrometría de Masas , Microscopía Electrónica de Rastreo , MicroesferasRESUMEN
INTRODUCTION: The primary analysis of a global phase 3 study that evaluated the efficacy and safety of denosumab versus zoledronic acid for preventing skeletal-related events (SREs) in adults with newly diagnosed multiple myeloma (MM) indicated that denosumab was noninferior to zoledronic acid for time to first on-study SREs. Here we present a subgroup analysis to evaluate efficacy and safety in Asian patients. METHODS: Patients were randomized 1:1 to receive denosumab 120 mg subcutaneously or zoledronic acid intravenously 4 mg every 4 weeks in a double-blind, double-dummy fashion. All patients received standard-of-care first-line antimyeloma treatment. Each patient received either study drug until an estimated 676 patients experienced at least one on-study SRE and the primary efficacy and safety analyses were completed. RESULTS: Of 1718 total enrolled patients, 196 Asian patients (denosumab, n = 103; zoledronic acid, n = 93) were included in this subgroup analysis. Fewer patients in the denosumab group developed first on-study SRE compared with the zoledronic acid group; the crude incidence of SREs at the primary analysis cutoff was 38.8% and 50.5%, respectively (HR [95% CI], 0.77 [0.48-1.26]). All 194 patients receiving at least one dose of study drug experienced at least one treatment-emergent AE. The most common AEs reported in either group (denosumab, zoledronic acid) were diarrhea (51.0%, 51.1%), nausea (42.2%, 46.7%), and pyrexia (38.2%, 41.3%). Treatment-emergent renal toxicity occurred in 9/102 (8.8%) and 20/92 (21.7%) patients, respectively. Similar rates of positively adjudicated osteonecrosis of the jaw (7 [6.9%] vs 5 [5.4%]) and treatment-emergent hypocalcemia (19 [18.6%] vs 17 [18.5%]) were reported in the denosumab and zoledronic acid groups, respectively. CONCLUSION: Efficacy and safety outcomes from this Asian subgroup were comparable to those of the full study population. Overall, this analysis supports denosumab as an additional treatment option for standard of care for Asian patients with newly diagnosed MM with lytic bone lesions. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01345019.
Asunto(s)
Conservadores de la Densidad Ósea/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/etiología , Denosumab/uso terapéutico , Mieloma Múltiple/complicaciones , Resultado del Tratamiento , Ácido Zoledrónico/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Pueblo Asiatico/estadística & datos numéricos , Conservadores de la Densidad Ósea/administración & dosificación , Denosumab/efectos adversos , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Radix Salvia Miltiorrhiza (Danshen) and Radix Pueraria Lobate (Gegen) are officially listed in the Chinese Pharmacopoeia and have long been used together as a Compound Chinese Traditional Medicine (CCTM) for treatment of coronary heart diseases, which are often co-administered with aspirin or warfarin to patients suffering from cardiovascular diseases. AIM OF STUDY: Since significant pharmacokinetic and pharmacodynamic interactions between Danshen-Gegen (DG) formula and aspirin/warfarin have been observed in our previous rat studies, the current study was proposed aiming to further verify such pharmacokinetic and pharmacodynamic interactions in healthy human subjects and explore related mechanisms. MATERIALS AND METHODS: A 5-day, multiple dose, five-session clinical trial has been carried out (n = 14) with 2-week washout periods between sessions, during which the subjects would receive different combinations of the medications. Plasma samples were collected for pharmacokinetic evaluation, and whole blood samples were collected for pharmacodynamic evaluation. In addition, an in-vitro mechanistic study is conducted to investigate the role of danshensu on the anti-thrombotic and anti-platelet aggregation effects of warfarin and aspirin respectively. RESULTS: Significant pharmacokinetic and pharmacodynamic herb-drug interactions were observed in healthy human subjects. pharmacokinetically, co-administration of DG with aspirin or warfarin could lead to a moderately increased AUC0ât of aspirin and a decreased AUC0ât of 7-hydroxyl warfarin respectively. The systemic exposure of danshensu (DSS, the marker component of DG) would be significantly increased after co-administration with warfarin. Pharmacodynamically, a reduction in systemic thromboxane B2 concentration was noticed after administration of DG with aspirin, which could be associated with the increased systemic exposure of aspirin and the synergistic effect of danshensu, aspirin and salicylic acid on cyclooxygenase (COX) inhibition. An offset on the warfarin induced soluble thrombomodulin induction was observed after its co-administration with DG, which could be partially attributed to the COX-2 inhibition effect of danshensu. CONCLUSION: Our results indicated that co-administration of DG with aspirin/warfarin would lead to significant pharmacokinetic and pharmacodynamic herb-drug interactions in healthy human subjects.